TY - JOUR
T1 - Design, Synthesis, Molecular Docking, and Anticancer Activity of Chalcone Derivatives as VEGFR-2 Inhibitors
AU - Yu, Mingjun
AU - Zhang, Xin
AU - Zhu, Hui
AU - Zhang, Xiaoqian
N1 - Funding information:
This work was supported by Bozhou University Research Initiation Program, grant number BYKQ202417; Bozhou University Enterprise Cooperation Project, grant number BYH2025020; Bozhou University Teaching Reform Program, grant number 2022XJXM057; and Anhui Province University Science and Engineering Teachers’ Internship Program in Enterprises, grant number 2024jsqygz135.
Publisher Copyright:
© 2025 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2025/12/1
Y1 - 2025/12/1
N2 - A series of 4-phenylurea chalcones (2a–2s) as VEGFR-2 inhibitors has been designed, synthesized, and evaluated for in vitro cytotoxic activity against K562, SiHa, and B16 cancer cells. Compared to sorafenib, the compounds exhibited strong cytotoxicity against K562, SiHa and B16 cells. Compounds 2r, 2o, and 2l exhibited remarkable cytotoxicity against K562, SiHa, and B16 cells, with IC50 values of 0.97 μM, 1.22 μM, and 1.39 μM, respectively. Moreover, compound 2l exhibited potent cytotoxicity against K562, SiHa, and B16, with IC50 values ranging from 1.25 μM to 1.39 μM. Compounds 2l and 2o also exhibited excellent inhibitory activity on VEGFR-2 kinase, with IC50 values of 0.42 ± 0.03 and 0.31 ± 0.02 μM, respectively. Molecular docking proved that the target compounds had strong binding interactions with VEGFR-2 proteins. Flow cytometry analysis showed that compound 2l induced apoptosis and arrested the cell cycle at the G1 and S phases.
AB - A series of 4-phenylurea chalcones (2a–2s) as VEGFR-2 inhibitors has been designed, synthesized, and evaluated for in vitro cytotoxic activity against K562, SiHa, and B16 cancer cells. Compared to sorafenib, the compounds exhibited strong cytotoxicity against K562, SiHa and B16 cells. Compounds 2r, 2o, and 2l exhibited remarkable cytotoxicity against K562, SiHa, and B16 cells, with IC50 values of 0.97 μM, 1.22 μM, and 1.39 μM, respectively. Moreover, compound 2l exhibited potent cytotoxicity against K562, SiHa, and B16, with IC50 values ranging from 1.25 μM to 1.39 μM. Compounds 2l and 2o also exhibited excellent inhibitory activity on VEGFR-2 kinase, with IC50 values of 0.42 ± 0.03 and 0.31 ± 0.02 μM, respectively. Molecular docking proved that the target compounds had strong binding interactions with VEGFR-2 proteins. Flow cytometry analysis showed that compound 2l induced apoptosis and arrested the cell cycle at the G1 and S phases.
KW - anticancer
KW - chalcone
KW - molecular docking
KW - urea fragment
KW - VEGFR-2
UR - https://www.scopus.com/pages/publications/105024597882
U2 - 10.3390/molecules30234526
DO - 10.3390/molecules30234526
M3 - Journal article
C2 - 41375124
AN - SCOPUS:105024597882
SN - 1420-3049
VL - 30
JO - Molecules
JF - Molecules
IS - 23
M1 - 4526
ER -
